Aggressive radiotherapy dose de-escalation confers benefits in HPV-associated oropharyngeal squamous cell carcinoma

Aggressively de-escalated adjuvant radiotherapy for patients with HPV-associated oropharynx squamous cell carcinoma produced local tumor control rates comparable to those of historical controls, according to results of a single-arm phase 2 study published in Journal of Clinical Oncology. The de-escalated treatment also was associated with decreased toxicity and slight improvement in swallowing function. “HPV-associated oropharyngeal squamous cell carcinoma represents a demographically and biologically distinct disease compared with historical head and neck squamous cell carcinomas,” Daniel J. Ma, MD, radiation oncologist at Mayo Clinic in Rochester, Minnesota, and colleagues wrote. “Patients are more likely to be younger and nonsmokers and have fewer medical comorbidities. Furthermore, in vitro and in vivo experiments have demonstrated that these tumors are more sensitive to radiotherapy and chemotherapy compared with historical head and neck squamous cell carcinomas.” The current standard treatment for HPV-associated oropharyngeal squamous cell carcinoma is 7 weeks of radiotherapy at 70 Gy in combination with cisplatin or surgery followed by a 6-week regimen of adjuvant radiotherapy at 60 Gy to 66 Gy with or without cisplatin. However, these approaches result in significant toxicities. The two-cohort study by Ma and colleagues included 79 patients (mean age, 58.7 years; 89.9% men) with p16-positive oropharyngeal squamous cell carcinoma who had a smoking history of 10 years or less and negative margins. Patients in cohort A (n = 36) received 30 Gy delivered in 1.5-Gy fractions twice daily for 2 weeks in combination with 15 mg/m2 docetaxel once per week. Cohort B (n = 43), which included [...]

2019-07-29T16:20:52-07:00July, 2019|Oral Cancer News|

CDC: Top HPV-Associated Cancer Is Now Oropharyngeal

Date: 08/23/18 Source: medscape.com Author: Nick Mulcahy Oropharyngeal squamous cell carcinoma (SCC) is now the most common HPV-associated cancer in the United States, according to a new report from the Centers for Disease Control and Prevention (CDC) that covers the years 1999 to 2015. During that period, cervical cancer dropped from being the top HPV-associated cancer and oropharyngeal SCC took its place. The transition happened because cervical carcinoma incidence rates decreased 1.6% per year, and oropharyngeal SCC incidence rates increased 2.7% per year among men and 0.8% per year among women. In 2015, there were a total of 11,788 cervical cancers compared with 18,917 oropharyngeal SCCs. The decline in cervical cancer is a "continued trend since the 1950s as a result of cancer screening," write the report authors, led by Elizabeth Van Dyne, MD, MPH, an epidemic intelligence service officer at the CDC. The uptick in oropharyngeal SCC could be due in part to "changing sexual behaviors," including unprotected oral sex, especially among white men, who report having the highest number of sexual partners and performing oral sex at a younger age compared with other racial/ethnic groups, the authors say. Oropharyngeal SCCs include those at the base of tongue, pharyngeal tonsils, anterior and posterior tonsillar pillars, glos­sotonsillar sulci, anterior surface of soft palate and uvula, and lateral and posterior pharyngeal walls. The new report was published August 24 in the Morbidity and Mortality Weekly Report. The study authors defined HPV-associated cancer as "an invasive malignancy in which HPV DNA was frequently [...]

2019-01-02T13:54:33-07:00January, 2019|Oral Cancer News|

Less Is More for HPV Oropharyngeal Cancer Reduced-intensity regimen clears disease in 86% of cases

Source: www.medpagetoday.comAuthor: Charles Bankhead SAN ANTONIO -- Less intense treatment of low-risk human papillomavirus (HPV)-related oropharyngeal cancer achieved a high rate of pathologic complete response (pCR) and favorable patient-reported outcomes, a preliminary trial showed. Overall, 37 of 43 (86%) patients achieved pCR with deintensified chemoradiation, including all but one evaluable primary tumor. The pCR rate was virtually identical to historical rates achieved with standard regimens, according to Bhishamjit Chera, MD, of the University of North Carolina (UNC) at Chapel Hill, and colleagues. Selected patient-reported adverse events peaked during the first 6 to 8 weeks and then declined thereafter. About 40% of patients required feeding tubes for a median duration of 15 weeks, but no patients required permanent feeding tubes, they reported here at the American Society for Radiation Oncology meeting. The regimen consists of lower doses of radiotherapy and concurrent cisplatin, administered over 6 weeks. With high-dose therapy, the radiation protocol requires an additional week. "Though we have limited follow-up, the pathological complete response rate with this reduced-intensity chemoradiotherapy regimen is very high in patients with favorable-risk oropharyngeal squamous-cell carcinoma," Chera said. "The early quality-of-life measurements are encouraging, particularly the data on swallowing. We are optimistic that these results with reduced-intensity treatment will translate into good long-term disease control with less toxicity." The study reflects the current trend and momentum in the management of HPV-positive oropharyngeal cancer, said Zain Husain, MD, of Yale Cancer Center in New Haven, Conn. "This is the second study to show that de-escalation of therapy might [...]

2015-10-21T14:59:53-07:00October, 2015|Oral Cancer News|

HPV16 Antibodies Signal Even Better Oral Cancer Outcomes

Source: www.medscape.comAuthor: Neil Osterweil Another prognostic tool may be in the offing for clinicians to use in evaluating patients with oropharyngeal cancers, new research suggests. The presence in serum of three antibodies to human papillomavirus type 16 (HPV16) was predictive of better progression-free and overall survival in these patients, according to Kristina R. Dahlstrom, PhD, from the University of Texas MD Anderson Cancer Center, in Houston, and colleagues. Patients whose serum was positive for the presence of three specific antibodies to "early" (E) proteins involved in replication and growth of HPV16 had dramatically better rates of overall survival (OS) and progression-free survival (PFS) compared with patients whose serum was negative for the antibodies, they reported online June 15 in Clinical Cancer Research. Specifically, for those patients whose serum was positive for any E antibodies, 5-year estimated OS was 87.4%, compared with 42.2% for patients whose sereum was negative for all E antibodies (P < .001). The respective 5-year PFS rates were 82.9% and 46.1% (P < .001). "These results hint at a prognostic stratification of patients with HPV-related oropharynx cancer reflecting humoral immune response to HPV type 16 E proteins and thus may help in choosing immunotherapy approaches for such patients in future," said senior author Erich M. Sturgis, MD, MPH, a surgeon at MD Anderson, in comments to Medscape Medical News. Currently, the serology results are not strong enough to be used as clinical decision tools for choosing current therapies, she added. Their findings also suggest that vaccine-based immunotherapy targeted [...]

Robotic Surgery Is Useful Option for Oral Cancer

Source: Onclive.com Minimally invasive transoral robotic surgery (TORS), used alone or combined with adjuvant therapy, provides good functional and oncologic outcomes in patients with oropharyngeal squamous cell carcinoma (OPSCC), new research suggests. The results were especially impressive in patients with human papillomavirus (HPV) infection, which is currently the most common cause of OPSCC in Europe and the United States. Eric J. Moore, MD, associate professor of Otolaryngology at the Mayo Clinic in Rochester, Minnesota, and coauthors reviewed a prospective database of patients with previously untreated OPSCC arising in the tonsil or base of the tongue who underwent TORS at their institution during a recent 2-year period. In 2011, about 12,000 individuals in the United States were diagnosed with OPSCC, according to the authors. The most common sites are the tonsillar fossa and base of the tongue. Customarily, OPSCC has been treated with combined modality therapy, including open surgical resection through mandibulotomy, neck dissection, and adjuvant radiation therapy or combined chemotherapy and radiation therapy. TORS was later introduced to improve access to these tumors. Functional outcomes of the study included gastrostomy tube dependence and tracheostomy dependence. Oncologic outcomes included local, regional, and distant control and disease-specific and recurrence-free survival. Overall, 66 patients who underwent TORS as their primary treatment were followed for a minimum of 2 years. Sixty-four patients, or 97%, were able to tolerate an oral diet and maintain their nutritional needs before initiating adjuvant therapy at 4 weeks. Only 3 patients, or 4.5%, required long-term gastrostomy tube use, and [...]

2012-04-30T17:14:50-07:00April, 2012|Oral Cancer News|

New Throat Cancer Gene Uncovered

Source: Science Daily Researchers at King's College London and Hiroshima University, Japan, have identified a specific gene linked to throat cancer following a genetic study of a family with 10 members who have developed the condition. The study, published March 8 in the American Journal of Human Genetics, uncovered a mutation in the ATR gene, demonstrating the first evidence of a link between abnormality in this gene and an inherited form of cancer. The researchers say this finding raises new ideas about genetic factors linked to throat cancer and provides a platform for exploring the role of ATR more generally in cancer biology. Scientists carried out a genome-wide linkage study in a US family with an unusual hereditary condition affecting 24 members of the family over five generations. Characteristics include developmental abnormalities of hair, teeth and nails as well as dilated skin blood vessels. Strikingly, nearly every person with the condition involved in the study had developed throat cancer (oropharyngeal squamous cell carcinoma) in their 20s or 30s. The team took blood samples from 13 members of the affected family, as well as samples from 13 unaffected people. After analysing these samples they found a single mutation in ATR was present in all the people with the condition, but none of the unaffected people had the mutation. Ten of the 13 people with the condition had developed throat cancer. Professor John McGrath from the King's College London Genetic Skin Disease Group at St John's Institute of Dermatology, based at Guy's [...]

2012-03-09T15:03:16-07:00March, 2012|Oral Cancer News|

Connected nodes in throat cancer signal poor prognosis

Source: OncologyNurseAdvisor.com The presence of “matted” lymph nodes in persons with oropharyngeal squamous cell carcinoma (SCC)—that is, nodes that are connected together—was associated with a 3-year survival rate of 69%, compared with 94% among patients without matted nodes. Such a marker could help clinicians identify patients who are at heightened risk for metastasis and who might benefit from additional systemic therapy. Conversely, a person without matted nodes could be a candidate for less therapy, which would in turn reduce uncomfortable side effects. The study, led by Matthew E. Spector, MD, a resident in the department of otolaryngology – head and neck surgery at the University of Michigan Health System in Ann Arbor, focused on 78 previously untreated persons with stage III or IV oropharyngeal SCC. All patients were undergoing chemotherapy in combination with intensity-modulated radiation therapy (IMRT) as part of a clinical trial. The 3-year disease-specific survival rate for the 16 patients presenting with matted nodes was 69%, compared with 94% among the 61 other patients. Matted nodes were found to be a poor prognostic factor independent of tumor classification, human papillomavirus (HPV) status, epidermal growth factor receptor (EGFR), and smoking status. Matted nodes did appear to be an especially strong indicator of increased risk among HPV-positive persons, despite the fact that these patients had better overall outcomes than did those who were HPV-negative. The best outcomes were seen among HPV-positive nonsmokers. The investigators, who reported their findings in Head & Neck, say the reasons for the survival differences between [...]

2012-02-01T17:10:52-07:00February, 2012|Oral Cancer News|

Implications of the Oropharyngeal Cancer Epidemic

Source: Journal of Clinical Oncology Chaturvedi et al,1 analyzing specimens back to 1984, validate the long-held hypothesis that infection with human papillomavirus (HPV) has increased oropharyngeal squamous cell carcinoma (OPSCC) incidence in the US. They find the incidence of OPSCC in men—who have higher risks of both HPV-positive and HPV-negative OPSCC than women—similar to that of cervical cancer in women. From 1988 to 2004, incidence of HPV-negative OPSCC decreased in parallel with smoking whereas incidence of HPV-positive OPSCC increased at about 7.5% per year, so the percentage of OPSCC that was HPV-positive went from less than 20% to more than 70%. HPV-positive and HPV-negative OPSCC are etiologically and clinically distinct,2,3 with HPV-positive disease having better outcome.4–6 In the current study,1 the hazard ratio of 0.3 for HPV-positive/HPV-negative in survival analysis essentially balances the difference in prevalence so each form of OPSCC now accounts for a similar number of deaths. Notably, the authors found that outcomes for HPV-positive OPSCC have improved over time, whereas outcomes for HPV-negative OPSCC are as dismal as they were 25 years ago. The authors argue convincingly that vaccination to prevent oral HPV infections should be evaluated and that better treatments for both types of OPSCC should be developed. We are unlikely to get a better picture of the recent history of OPSCC in the United States. This study used all available OPSCC specimens from the three Surveillance, Epidemiology, and End Results (SEER) registries that participate in the Residual Tissue Repositories Program, analyzed them in several ways, [...]

2011-11-09T15:24:59-07:00November, 2011|Oral Cancer News|

Evaluation of Human Papilloma Virus Diagnostic Testing in Oropharyngeal Squamous Cell Carcinoma: Sensitivity, Specificity, and Prognostic Discrimination

Source: Clinical Cancer Research Abstract Purpose: Human papillomavirus-16 (HPV16) is the causative agent in a biologically distinct subset of oropharyngeal squamous cell carcinoma (OPSCC) with highly favorable prognosis. In clinical trials, HPV16 status is an essential inclusion or stratification parameter, highlighting the importance of accurate testing. Experimental Design: Fixed and fresh-frozen tissue from 108 OPSCC cases were subject to eight possible assay/assay combinations: p16 immunohistochemistry (p16 IHC); in situ hybridization for high-risk HPV (HR HPV ISH); quantitative PCR (qPCR) for both viral E6 RNA (RNA qPCR) and DNA (DNA qPCR); and combinations of the above. Results: HPV16-positive OPSCC presented in younger patients (mean 7.5 years younger, P = 0.003) who smoked less than HPV-negative patients (P = 0.007). The proportion of HPV16-positive cases increased from 15% to 57% (P = 0.001) between 1988 and 2009. A combination of p16 IHC/DNA qPCR showed acceptable sensitivity (97%) and specificity (94%) compared with the RNA qPCR “gold standard”, as well as being the best discriminator of favorable outcome (overall survival P = 0.002). p16 IHC/HR HPV ISH also had acceptable specificity (90%) but the substantial reduction in its sensitivity (88%) impacted upon its prognostic value (P = 0.02). p16 IHC, HR HPV ISH, or DNA qPCR was not sufficiently specific to recommend in clinical trials when used in isolation. Conclusions: Caution must be exercised in applying HPV16 diagnostic tests because of significant disparities in accuracy and prognostic value in previously published techniques. This news story was resourced by the Oral Cancer Foundation, and [...]

New Improved HPV Diagnostic Test for Head and Neck Cancer

Source: EurekAlert! Philadelphia -- Researchers have determined that a combination of P16 immunohistochemistry and DNA qPCR to test for viral E6 can accurately determine the oropharyngeal squamous cell carcinoma, a form of head and neck cancer, which derive from HPV16, according to a study published in Clinical Cancer Research, a journal of the American Association for Cancer Research. "This has immediate clinical applications as we consider recruitment to clinical trials designed to de-escalate the intensity of therapy based on HPV status" said lead researcher Andrew Schache, D.D.S., M.D., research fellow and surgeon at the University of Liverpool. Schache said that the attention surrounding HPV, particularly in the last several years, has given rise to a number of diagnostic tests, but the evaluation of these tests has lagged behind. For the current study, Schache and colleagues evaluated eight possible combinations of known diagnostic tests on 108 cases of HPV16 derived oropharyngeal squamous cell carcinoma. They used viral gene expression as the standard marker. "Viral gene expression has 100 percent specificity and sensitivity, but it requires very high quality tissue that is often not available," said Schache. After evaluating the tests, they found that a combination of DNA qPCR and P16 immunohistochemistry had 97 percent sensitivity, a measure of accurate positive tests, and 94 percent specificity, a measure of accurate negative tests. Both of these assays are commercially available in proprietary and generic forms, Schache said, so the combination test could be administered. "Getting the diagnosis right is extremely important because cases [...]

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